EP300 facilitates human trophoblast stem cell differentiation

生物 滋养层 细胞滋养层 胎盘形成 细胞分化 细胞生物学 癌症研究 遗传学 胎盘 胎儿 基因 怀孕
作者
A. Jantine van Voorden,Remco Keijser,Geertruda J. M. Veenboer,Solange A. Lopes Cardozo,Dina Diek,Jennifer A. Vlaardingerbroek,Marie van Dijk,Carrie Ris‐Stalpers,Ans M. M. van Pelt,Gijs Afink
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [National Academy of Sciences]
卷期号:120 (28) 被引量:12
标识
DOI:10.1073/pnas.2217405120
摘要

Early placenta development involves cytotrophoblast differentiation into extravillous trophoblast (EVT) and syncytiotrophoblast (STB). Defective trophoblast development and function may result in severe pregnancy complications, including fetal growth restriction and pre-eclampsia. The incidence of these complications is increased in pregnancies of fetuses affected by Rubinstein–Taybi syndrome, a developmental disorder predominantly caused by heterozygous mutations in CREB-binding protein ( CREBBP ) or E1A-binding protein p300 ( EP300 ). Although the acetyltransferases CREBBP and EP300 are paralogs with many overlapping functions, the increased incidence of pregnancy complications is specific for EP300 mutations. We hypothesized that these complications have their origin in early placentation and that EP300 is involved in that process. Therefore, we investigated the role of EP300 and CREBBP in trophoblast differentiation, using human trophoblast stem cells (TSCs) and trophoblast organoids. We found that pharmacological CREBBP/EP300 inhibition blocks differentiation of TSCs into both EVT and STB lineages, and results in an expansion of TSC-like cells under differentiation-inducing conditions. Specific targeting by RNA interference or CRISPR/Cas9-mediated mutagenesis demonstrated that knockdown of EP300 but not CREBBP, inhibits trophoblast differentiation, consistent with the complications seen in Rubinstein–Taybi syndrome pregnancies. By transcriptome sequencing, we identified transforming growth factor alpha (TGFA, encoding TGF-α) as being strongly upregulated upon EP300 knockdown. Moreover, supplementing differentiation medium with TGF-α, which is a ligand for the epidermal growth factor receptor (EGFR), likewise affected trophoblast differentiation and resulted in increased TSC-like cell proliferation. These findings suggest that EP300 facilitates trophoblast differentiation by interfering with at least EGFR signaling, pointing towards a crucial role for EP300 in early human placentation.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
量子咸鱼K完成签到,获得积分10
刚刚
胡思乱想完成签到,获得积分10
刚刚
hahaha6789y完成签到,获得积分10
1秒前
Galri完成签到 ,获得积分10
1秒前
秦含光完成签到,获得积分10
4秒前
maybe完成签到,获得积分10
4秒前
hahaha2完成签到,获得积分10
4秒前
小g完成签到,获得积分10
5秒前
徐彬荣完成签到,获得积分10
6秒前
李栖迟完成签到 ,获得积分10
6秒前
Adamcssy19完成签到,获得积分10
7秒前
脑洞疼应助科研通管家采纳,获得10
7秒前
霡霂完成签到,获得积分10
8秒前
XU博士完成签到,获得积分10
8秒前
hahaha1完成签到,获得积分10
8秒前
豆子完成签到 ,获得积分10
11秒前
蔡一完成签到,获得积分10
13秒前
奋斗的妙海完成签到 ,获得积分0
16秒前
梅子发布了新的文献求助10
17秒前
风清扬应助喂我采纳,获得200
20秒前
细心青雪完成签到 ,获得积分10
23秒前
zjq完成签到 ,获得积分10
24秒前
贤惠的老黑完成签到 ,获得积分10
30秒前
sunny完成签到 ,获得积分10
35秒前
江水居士完成签到,获得积分10
35秒前
左丘冬寒完成签到,获得积分10
37秒前
Curry完成签到 ,获得积分10
41秒前
甜甜以云完成签到,获得积分10
44秒前
啊哈啊哈额完成签到,获得积分10
49秒前
yzx完成签到 ,获得积分10
49秒前
52秒前
papi发布了新的文献求助10
56秒前
北方有相思完成签到 ,获得积分10
59秒前
梅子完成签到,获得积分10
59秒前
又村完成签到 ,获得积分10
1分钟前
gao完成签到 ,获得积分0
1分钟前
LJJ完成签到 ,获得积分10
1分钟前
优雅莞完成签到,获得积分10
1分钟前
缥缈的觅风完成签到 ,获得积分10
1分钟前
干净思远完成签到,获得积分10
1分钟前
高分求助中
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
Beauty and Innovation in La Machine Chinoise: Falla, Debussy, Ravel, Roussel 1000
Rapid Review of Electrodiagnostic and Neuromuscular Medicine: A Must-Have Reference for Neurologists and Physiatrists 1000
An overview of orchard cover crop management 800
基于3um sOl硅光平台的集成发射芯片关键器件研究 500
National standards & grade-level outcomes for K-12 physical education 400
Research Handbook on Law and Political Economy Second Edition 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 内科学 生物化学 物理 计算机科学 纳米技术 遗传学 基因 复合材料 化学工程 物理化学 病理 催化作用 免疫学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 4806949
求助须知:如何正确求助?哪些是违规求助? 4122062
关于积分的说明 12752912
捐赠科研通 3856609
什么是DOI,文献DOI怎么找? 2123410
邀请新用户注册赠送积分活动 1145479
关于科研通互助平台的介绍 1037923